Clinical manifestations of cutaneous aging include dry skin, scaly skin, discoloration of skin, fine lines and wrinkles, enlarged pores, dermal thinning, sagging of the skin and loss of elasticity in the skin. Clinical examinations, bioengineering tools and biochemical analysis allow one to quantitatively assess the onset of these manifestations with age.
Human skin is affected by exogenous or endogenous factors, many of which are deteriorative, while some are presumed to be beneficial. Skin aging may be thought of as the accumulation of damage with time. In skin, this damage may be the result of normal physiological processes, environmental factors, genetic dispositions, lifestyle choices and use of topical preparations.
Environmental factors include: sun exposure, pollution, second hand smoke, gravity, irritants, etc. Lifestyle choices include: diet, exercise, amount of sleep, smoking, occupational hazards, mechanical manipulation (i.e. massage), etc. Genetic disposition may include vitamin or mineral deficiency or disease. Topical preparations include: cosmetics, dermatologics, and pharmaceuticals. Still other factors affecting skin aging include trauma, mental stress and medical intervention. Some of these factors trigger an inflammatory response, which may release free radicals into the skin. Free radicals play a deteriorative role in skin aging. Other of these factors favor the non-enzymatic glycation of proteins and/or cause other glyco-oxidative damage in the skin. Structural changes in the skin that are associated with some of these factors, include the deterioration of collagen and elastin networks in the surface layers of the skin. This deterioration causes loss of skin elasticity and firmness. The cumulative impact of these factors is a deterioration of the external appearance of the skin. The rate of deterioration of the skin's appearance will vary from individual to individual, however, the cardinal signs of skin deterioration may be the formation of lines and wrinkles, sagging skin and age spots. The emergence of these signs may cause a person to appear older than his or her chronological age would suggest. For example, it has been reported that the estimated or apparent age of smokers is higher than non-smokers (Kennedy et al, 2003); and the estimated or apparent age of middle aged women who had more sun exposure is higher than that of middle aged women with less sun exposure (Warren et al, 1991). Also, higher intakes of vitamin C and lower intakes of fats and carbohydrates have been associated with better skin-aging appearance (Cosgrove et al, 2007).
Different Measures of Age
By “chronological age”, we mean a person's actual life span. By “apparent age” or “perceived age” we mean the age that a person is visually estimated to be, based on their physical appearance, particularly the overall appearance of the face. Chronological age and apparent age are generally measured in years and parts thereof.
One goal of anti-aging skin care products is to reduce apparent age relative to chronological age, preferably reducing apparent age below chronological age, so that a person appears younger than their actual life span. Products that achieve this goal are able to prevent skin damage and/or remove the damage induced by age-promoting factors.
1. Subjective Apparent Age
Apparent age is used consciously or subconsciously, all the time, as part of normal social interaction, and each of us is subject to assessment by others, based on an apparent age. The problem is, this type of apparent age is subjective, being based on social norms and expectations. This subjectivity makes it impossible to apply consistently and uniformly so that different observers may estimate widely different ages for the same individual. Thus, any evaluation of the effectiveness of a skin care product that alters the skin to appear younger, is subjective and defies precise quantification, when only a subjective apparent age is used to make the evaluation. This makes it very difficult to compare the efficacy of one treatment regimen to another or one treatment regimen on different individuals.
Likewise, when only subjective apparent age is used, the deteriorative effects of various factors that alter the skin to appear older, defy precise quantification. This makes it difficult or impossible to compare the deteriorative effects one to another, or in different individuals. If each skin-deteriorating factor affected all individuals the same, then the apparent age of an individual would correlate closely with his/her chronological age. This however, is not always the case. Thus, it would be better to have an objective method of assessing the physical appearance of skin, that more closely correlates with chronological age. A need exists therefore, for a meaningful, objective quantification of age, that can be used to predict or explain the apparent age of an individual, that can be used to evaluate treatment efficacy and/or deteriorative factors, and that can be used to predict changes in apparent age. Sometimes, apparent age is estimated by a trained or expert clinician. While this removes some of the subjectivity, experience has shown that a need still exists for a determination of apparent age with a greater degree of objectivity, consistency and repeatability than heretofore achieved.
2. Objective Apparent Age
By “objective apparent age” we mean the age that a person is estimated to be, based measurements of several relevant parameters. The measurements may be made by instrumentation and/or made by observation by an expert clinician. Objective apparent age has significantly less subjective component than conventional apparent age, and objective apparent age can be applied more consistently and uniformly. Therefore, it would be preferable to use an objective apparent age to predict or explain the apparent age of an individual and to evaluate the effectiveness of a product or treatment regimen or the effect of age-related factors.
3. Parameters Used To Evaluate Age
To be truly useful, the number of relevant parameters that are used to compute an objective apparent age must not be excessive; the parameters must be measurable by well defined, repeatable procedures; and the set of measurements must account for all or a statistically significant amount of the observed skin ageing. One problem is that hundreds of such parameters may be and have been proposed. Thus, a need remains for an objective assessment of physical appearance, based on a relatively small number of critical parameters combined in a way that accounts for all or most of the apparent skin ageing. We call this objective assessment the Objective Apparent Age Score (OAAS), and it is new in the art.
In general, parameters used to quantify physical appearance may be clinical, biophysical or biochemical, in nature, although test subject feedback may also be considered. Once a set of parameters is chosen and measured, the measurements must be combined in a meaningful way to yield an Objective Apparent Age Score. A well chosen set of parameters, properly combined will yield an objective, consistent and repeatable measurement of physical appearance, regardless of which age-promoting factors are present in an individual or population. Such a set of parameters and the rules for combining them may be used to evaluate the effectiveness of treatment or predict outcomes of treatment. It may also guide the development of new treatments and products, by identifying which parameters are most critical. Thus, an Objective Apparent Age Score, herein defined, is foremost, a model for understanding a person's apparent age, which is to say, identifying the factors that most increase a person's apparent age.
As noted, at least three types of measurements can be made; clinical assessment by expert clinician (which may be visual or tactile); biophysical assessment by instrumentation; and biochemical assessment by instrumentation. A fourth source of information is test subject feedback or psychological feedback.
Parameters In The Prior Art
One example of the use of clinical parameters to arrive at an apparent age is to use a validated Skin Age Score by combining measured values of visual and tactile parameters of facial skin features (see Guinot et at 2002: Relative contribution of intrinsic and extrinsic factors to skin aging as determined by a validated Skin Age Score. Arch Dermatol. 138:1454-1460). In the study, 62 characteristics of facial skin of 361 white women, aged 18 to 80 years, were assessed by clinical analysis (CA). Ultimately, 24 characteristics were identified as having a linear link with chronological age and only these were retained. Thus, the purpose of this study was to find a connection between a clinical assessment of skin age and chronological age. The Skin Age Score constructed on the basis of these 24 characteristics did show a linear relationship with chronological age, but individual discrepancies between Skin Age Score and chronological age could not be explained. For example, the authors were able to report that skin phototype, body mass index, menopausal status, degree of lifetime sun exposure and number of year of cigarette smoking could account for only 10% of the discrepancies between Skin Age Score and chronological age. Thus, in quantifying apparent age, the exclusive use of these 24 clinical parameters appears to be insufficient to account for chronological age. Ultimately, the authors conclude, “Because recognized environmental, lifestyle, and biological factors explained only approximately 10% of the discrepancies between the SAS and chronological age, it is indeed warranted to search for such additional factors contributing to aging.” In contrast, the present invention is not concerned with a connection between a clinically assessed apparent age and chronological age. However, the methods of the present invention advantageously include some of the clinical markers of the Guinot et al study, while discarding others and identifying new parameters for inclusion.
It has been suggested that non-visually assessable, biophysical parameters, such as skin firmness, skin elasticity, skin density or skin texture, may play a role in objectively evaluating apparent age. Various non-visual parameters can be measured with existing bioinstrumentation methods (see Waller and Maibach, 2005: Age and skin structure and function, a quantitative approach (I): blood flow, pH, thickness, and ultrasound echogenicity. Skin Res Technol. 11: 221-235; also see, Waller and Maibach, 2006: Age and skin structure and function, a quantitative approach (II): protein, glycosaminoglycan, water, and lipid content and structure. Skin Res Technol. 12: 145-514). However, the variation with age, of these non-visual parameters, seems to be affected by large inter-individual variations. The methods of the present invention advantageously include some of these biophysical markers in quantifying the apparent age of an individual, while discarding others.
Certain biochemical parameters that are causally related to changes in skin condition, can also be expected to correlate with apparent age. For example, biochemical mechanisms leading to impairment of dermal and epidermal structures have been analyzed. It has been concluded that that free radical-mediated oxidative reactions caused by an inflammatory response, are an underlying cause of accelerated aging of the dermis (see Giacomoni, 2005: Ageing, science and the cosmetics industry. The micro-inflammatory model serves as a basis for developing effective anti-ageing products for the skin. EMBO Rep. 6 Spec No:S45-S48; and Giacomoni and Rein, 2001: Factors of skin ageing share common mechanisms. Biogerontology 2: 219-229).
Other biochemical factors can provoke lentigo senilis and other discolorations. Also, the accumulation of sugar in the body and the devastating effect of glycation have been clearly demonstrated (Monnier 1989: Toward a Maillard reaction theory of aging. Prog Clin Biol Res. 304: 1-22; and Dyer et al, 1993: Accumulation of Maillard reaction products in skin collagen in diabetes and aging. J Clin Invest. 91: 2463-2469). It has also been shown that advanced glycation end-products promote the synthesis of V-CAM 1 and are therefore pro-inflammatory (Schmidt et al, 1995: Advanced glycation end products interacting with their endothelial receptor induce expression of V-CAM 1 in cultured human endothelial cells and in mice J. Clin. Invest. 96: 1395-1403). The methods of the present invention advantageously include some of these biochemical markers in quantifying the apparent age of an individual, while discarding others.
It must be borne in mind, that just because a biological process or biophysical presentation is known to have an effect on the appearance of the skin, that does not mean that such a process or presentation should be included in an objective, predictive model of apparent age. The reason is, the process or presentation may not be a driver of apparent age. There may be a deeper underlying factor. Thus, there remains a need for an accurate, objective model of the apparent age of the human skin. The present invention identifies deeper, underlying factors, while omitting some parameters that, at first, may seem obvious to include.